Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach

Epstein-Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of Plasmodium falciparum in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both infections in the development of eBL by investigating the IgG and IgM profiles...

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Autores: Aguilar, Ruth, Casabonne, Delphine, O’Callaghan-Gordo, Cristina, Vidal, Marta, Campo, Joseph J., Mutalima, Nora, Angov, Evelina, Dutta, Sheetij, Gaur, Deepak, Chitnis, Chetan E., Chauhan, Virander, Michel, Angelika, de Sanjosé, Silvia, Waterboer, Tim, Kogevinas, Manolis, Newton, Rob, Dobaño, Carlota
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/34721
Acceso en línea:http://hdl.handle.net/10230/34721
http://dx.doi.org/10.3389/fimmu.2017.01284
Access Level:acceso abierto
Palabra clave:Virus d&apos
Epstein-Barr
Infeccions per virus d&apos
Infants -- Malalties -- Àfrica
Burkitt, Limfoma de
Epstein–Barr virus
Africa
IgG
IgM
Plasmodium falciparum
Children
Endemic Burkitt lymphoma
Multiplex
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spelling Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological ApproachAguilar, RuthCasabonne, DelphineO’Callaghan-Gordo, CristinaVidal, MartaCampo, Joseph J.Mutalima, NoraAngov, EvelinaDutta, SheetijGaur, DeepakChitnis, Chetan E.Chauhan, ViranderMichel, Angelikade Sanjosé, SilviaWaterboer, TimKogevinas, ManolisNewton, RobDobaño, CarlotaVirus d&aposEpstein-BarrInfeccions per virus d&aposEpstein-BarrInfants -- Malalties -- ÀfricaBurkitt, Limfoma deEpstein–Barr virusAfricaIgGIgMPlasmodium falciparumChildrenEndemic Burkitt lymphomaMultiplexEpstein-Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of Plasmodium falciparum in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both infections in the development of eBL by investigating the IgG and IgM profiles against several EBV and P. falciparum antigens. Serum samples collected in a childhood study in Malawi (2005-2006) from 442 HIV-seronegative children (271 eBL cases and 171 controls) between 1.4 and 15 years old were tested by quantitative suspension array technology against a newly developed multiplex panel combining 4 EBV antigens [Z Epstein-Barr replication activator protein (ZEBRA), early antigen-diffuse component (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 subunit (VCA-p18)] and 15 P. falciparum antigens selected for their immunogenicity, role in malaria pathogenesis, and presence in different parasite stages. Principal component analyses, multivariate logistic models, and elastic-net regressions were used. As expected, elevated levels of EBV IgG (especially against the lytic antigens ZEBRA, EA-D, and VCA-p18) were strongly associated with eBL [high vs low tertile odds ratio (OR) = 8.67, 95% confidence interval (CI) = 4.81-15.64]. Higher IgG responses to the merozoite surface protein 3 were observed in children with eBL compared with controls (OR = 1.29, 95% CI = 1.02-1.64), showing an additive interaction with EBV IgGs (OR = 10.6, 95% CI = 5.1-22.2, P = 0.05). Using elastic-net regression models, eBL serological profile was further characterized by lower IgM levels against P. falciparum preerythrocytic-stage antigen CelTOS and EBV lytic antigen VCA-p18 compared with controls. In a secondary analysis, abdominal Burkitt lymphoma had lower IgM to EBV and higher IgG to EA-D levels than cases with head involvement. Overall, this exploratory study confirmed the strong role of EBV in eBL and identified differential IgG and IgM patterns to erythrocytic vs preerythrocytic P. falciparum antigens that suggest a more persistent/chronic malaria exposure and a weaker IgM immune response in children with eBL compared with controls. Future studies should continue exploring how the malaria infection status and the immune response to P. falciparum interact with EBV infection in the development of eBL.Frontiers201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/34721http://dx.doi.org/10.3389/fimmu.2017.01284reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésFrontiers in Immunology. 2017 Oct 26;8:1284Copyright © 2017 Aguilar, Casabonne, O’Callaghan-Gordo, Vidal, Campo, Mutalima, Angov, Dutta, Gaur, Chitnis, Chauhan, Michel, de Sanjosé, Waterboer, Kogevinas, Newton and Dobaño. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/347212026-06-12T07:21:37Z
dc.title.none.fl_str_mv Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
title Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
spellingShingle Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
Aguilar, Ruth
Virus d&apos
Epstein-Barr
Infeccions per virus d&apos
Epstein-Barr
Infants -- Malalties -- Àfrica
Burkitt, Limfoma de
Epstein–Barr virus
Africa
IgG
IgM
Plasmodium falciparum
Children
Endemic Burkitt lymphoma
Multiplex
title_short Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
title_full Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
title_fullStr Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
title_full_unstemmed Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
title_sort Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach
dc.creator.none.fl_str_mv Aguilar, Ruth
Casabonne, Delphine
O’Callaghan-Gordo, Cristina
Vidal, Marta
Campo, Joseph J.
Mutalima, Nora
Angov, Evelina
Dutta, Sheetij
Gaur, Deepak
Chitnis, Chetan E.
Chauhan, Virander
Michel, Angelika
de Sanjosé, Silvia
Waterboer, Tim
Kogevinas, Manolis
Newton, Rob
Dobaño, Carlota
author Aguilar, Ruth
author_facet Aguilar, Ruth
Casabonne, Delphine
O’Callaghan-Gordo, Cristina
Vidal, Marta
Campo, Joseph J.
Mutalima, Nora
Angov, Evelina
Dutta, Sheetij
Gaur, Deepak
Chitnis, Chetan E.
Chauhan, Virander
Michel, Angelika
de Sanjosé, Silvia
Waterboer, Tim
Kogevinas, Manolis
Newton, Rob
Dobaño, Carlota
author_role author
author2 Casabonne, Delphine
O’Callaghan-Gordo, Cristina
Vidal, Marta
Campo, Joseph J.
Mutalima, Nora
Angov, Evelina
Dutta, Sheetij
Gaur, Deepak
Chitnis, Chetan E.
Chauhan, Virander
Michel, Angelika
de Sanjosé, Silvia
Waterboer, Tim
Kogevinas, Manolis
Newton, Rob
Dobaño, Carlota
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Virus d&apos
Epstein-Barr
Infeccions per virus d&apos
Epstein-Barr
Infants -- Malalties -- Àfrica
Burkitt, Limfoma de
Epstein–Barr virus
Africa
IgG
IgM
Plasmodium falciparum
Children
Endemic Burkitt lymphoma
Multiplex
topic Virus d&apos
Epstein-Barr
Infeccions per virus d&apos
Epstein-Barr
Infants -- Malalties -- Àfrica
Burkitt, Limfoma de
Epstein–Barr virus
Africa
IgG
IgM
Plasmodium falciparum
Children
Endemic Burkitt lymphoma
Multiplex
description Epstein-Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of Plasmodium falciparum in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both infections in the development of eBL by investigating the IgG and IgM profiles against several EBV and P. falciparum antigens. Serum samples collected in a childhood study in Malawi (2005-2006) from 442 HIV-seronegative children (271 eBL cases and 171 controls) between 1.4 and 15 years old were tested by quantitative suspension array technology against a newly developed multiplex panel combining 4 EBV antigens [Z Epstein-Barr replication activator protein (ZEBRA), early antigen-diffuse component (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 subunit (VCA-p18)] and 15 P. falciparum antigens selected for their immunogenicity, role in malaria pathogenesis, and presence in different parasite stages. Principal component analyses, multivariate logistic models, and elastic-net regressions were used. As expected, elevated levels of EBV IgG (especially against the lytic antigens ZEBRA, EA-D, and VCA-p18) were strongly associated with eBL [high vs low tertile odds ratio (OR) = 8.67, 95% confidence interval (CI) = 4.81-15.64]. Higher IgG responses to the merozoite surface protein 3 were observed in children with eBL compared with controls (OR = 1.29, 95% CI = 1.02-1.64), showing an additive interaction with EBV IgGs (OR = 10.6, 95% CI = 5.1-22.2, P = 0.05). Using elastic-net regression models, eBL serological profile was further characterized by lower IgM levels against P. falciparum preerythrocytic-stage antigen CelTOS and EBV lytic antigen VCA-p18 compared with controls. In a secondary analysis, abdominal Burkitt lymphoma had lower IgM to EBV and higher IgG to EA-D levels than cases with head involvement. Overall, this exploratory study confirmed the strong role of EBV in eBL and identified differential IgG and IgM patterns to erythrocytic vs preerythrocytic P. falciparum antigens that suggest a more persistent/chronic malaria exposure and a weaker IgM immune response in children with eBL compared with controls. Future studies should continue exploring how the malaria infection status and the immune response to P. falciparum interact with EBV infection in the development of eBL.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/34721
http://dx.doi.org/10.3389/fimmu.2017.01284
url http://hdl.handle.net/10230/34721
http://dx.doi.org/10.3389/fimmu.2017.01284
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Frontiers in Immunology. 2017 Oct 26;8:1284
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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